The objectives of this research proposal are: 1) To characterize immunologically and ultrastructurally the large body of neglected malignant lymphomas of extra-nodal origin, 2) to relate the results to the clinico-pathological features of these neoplasms and, in so doing, to 3) eventually be able to clearly distinguish benign from malignant lymphoreticular proliferations that commonly occur in the ocular tissues, skin, gastrointestinal tract, salivary glands and other extra-nodal sites. Prospective immunologic analysis has shown that the extra-nodal lymphoid neoplasms are divisible into monoclonal and polyclonal proliferations. The monoclonal proliferations have been shown to be malignant by histologic criteria while the polyclonal proliferations have been shown to be benign and reactive. Two "by-products" of the above-described cell marker analysis of lymphoid neoplasms are 1) the observation that T lymphocyte acid alpha-naphthyl acetate esterase (ANAE) activity represents a T cell differentiation marker and 2) that the Ia antigens, preferentially expressed on normal B cells, are also useful in distinguishing neoplastic B and T cells and that both B and T cell neoplasms display phenotypic heterogeneity.